Yevgeniya Sannova

Background: Photodynamic therapy (PDT) leading to immunogenic cell death (ICD) may serve as a promising basis for the development of antitumor therapeutic strategies. However, the mechanisms of action of photoinduced ICD in primary tumor cultures, including human glioma, remain unexplored. Methods: In the present study, the features of regulated cell death induced by photodynamic therapy using a previously described ICD inducer, porphyrazine III (pz III), were investigated. Cell death was studied in 7 primary cultures of high-grade human gliomas (astrocytomas, oligodendrogliomas, and glioblastomas). Results: Accumulation of porphyrazine III was observed in the endoplasmic reticulum (ER), Golgi apparatus, lysosomes, and mitochondria; however, the distribution of the photosensitizer varied across different cultures. A narrow concentration window of porphyrazine III was established to effectively reach IC85, primarily inducing ferroptosis with contributions from apoptosis and necroptosis accompanied by superoxide anion generation and mitochondrial dysfunction. Conclusions: Given the immunogenic potential of ferroptosis, apoptosis and necroptosis we hypothesize that the induction of PDT using porphyrazine III in glioma will trigger immunogenic cell death.

Photodynamic therapy (PDT) occupies an important place in the arsenal of cancer treatment modalities; however, its efficacy is primarily limited by the local nature of its effects and by tumor cell resistance. The aim of this review is to analyze the fundamental principles and biological consequences of PDT, to summarize current data on the molecular and cellular mechanisms determining its efficacy, and to consider strategies for overcoming its limitations. Particular attention is paid to the mechanisms underlying resistance development and to the role of switching from non-immunogenic to immunogenic cell death in shaping the antitumor response. The potential integration of PDT with dendritic cell vaccination is considered a promising strategy for overcoming these limitations. The potential of vaccine-based approaches to activate specific antitumor immunity in aggressive cancers is highlighted, with emphasis on the advantages of dendritic cell vaccines in addressing the limitations of conventional PDT.